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Publication : Sequential phases of cortical specification involve Neurogenin-dependent and -independent pathways.

First Author  Schuurmans C Year  2004
Journal  EMBO J Volume  23
Issue  14 Pages  2892-902
PubMed ID  15229646 Mgi Jnum  J:93057
Mgi Id  MGI:3055655 Doi  10.1038/sj.emboj.7600278
Citation  Schuurmans C, et al. (2004) Sequential phases of cortical specification involve Neurogenin-dependent and -independent pathways. EMBO J 23(14):2892-902
abstractText  Neocortical projection neurons, which segregate into six cortical layers according to their birthdate, have diverse morphologies, axonal projections and molecular profiles, yet they share a common cortical regional identity and glutamatergic neurotransmission phenotype. Here we demonstrate that distinct genetic programs operate at different stages of corticogenesis to specify the properties shared by all neocortical neurons. Ngn1 and Ngn2 are required to specify the cortical (regional), glutamatergic (neurotransmitter) and laminar (temporal) characters of early-born (lower-layer) neurons, while simultaneously repressing an alternative subcortical, GABAergic neuronal phenotype. Subsequently, later-born (upper-layer) cortical neurons are specified in an Ngn-independent manner, requiring instead the synergistic activities of Pax6 and Tlx, which also control a binary choice between cortical/glutamatergic and subcortical/GABAergic fates. Our study thus reveals an unanticipated heterogeneity in the genetic mechanisms specifying the identity of neocortical projection neurons.
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